Childhood leukemia is the leading cancer in children worldwide, yet it is a rare disease compared to adult cancers. Its etiology remains largely unknown, mainly due to its biological diversity and the multifactorial etiology involving interactions between genetic and environmental factors. Previous studies often lacked adequate statistical power to investigate risk factors of childhood leukemia taking into account gene-environment interaction. This problem is further compounded when considering leukemia subtypes, i.e., acute lymphoid vs. myeloid leukemia and specific cytogenetic subtypes characterized by chromosome translocation(s). To overcome the sample size limitations of individual studies, the Childhood Leukemia International Consortium (CLIC) was recently established, including an international group of eleven research teams with the aim of sharing comparable data from ongoing case-control and family-based trio studies on childhood leukemia. The overall objectives of CLIC are to achieve greater power, especially for subtype analyses, replicate novel findings, and afford substantial cost savings through large collaborative efforts. As the first proof of principle for this consortium, this project proposes to conduct pooled analyses to evaluate the role of the use of folate supplements during pregnancy, maternal alcohol consumption (known to reduce folate bioavailability), and methylenetetrahydrofolate reductase (MTHFR) genetic variants in the development of childhood leukemia by histological and cytogenetic subtype, and to assess the interactions between these factors. To achieve these aims, we will combine data from six studies in Northern California, Canada, the United Kingdom, France, and Australia, resulting in over 3,300 cases and 4,400 controls. Data will be pooled centrally at the University of California, Berkeley and distributed to the investigators for specific analyses. Statistical analyses will take into consideration study heterogeneity using appropriate models. International collaborators will meet in person annually and will communicate by conference call to discuss the organization of the consortium and progress with data pooling and analyses. We also plan to establish a website that will publicize the activities of the consortium and facilitate communication between consortium members and the wider scientific community. Collaboration with the International Agency for Research on Cancer, which has extensive experience in establishing consortia, adds strength to this proposed joint research. Childhood leukemia is the leading cancer in children worldwide, yet it remains a rare disease. To overcome the limitation of studies with limited sample size, especially for rarer leukemia subtypes, the Childhood Leukemia International Consortium (CLIC) was recently established, including eleven international research teams, with the aim of sharing comparable data from ongoing studies on childhood leukemia. We propose to evaluate the role of maternal folate intake, maternal alcohol consumption, and genes involved in folate metabolism, and to assess the interactions between these factors by combining data from six case-control studies of childhood leukemia in Northern California, Canada, the United Kingdom, France, and Australia, resulting in over 3,300 cases and 4,400 controls. Through this joint research, we plan to elucidate the etiologic role of folate and specific genes, while establishing a proof of principle for the consortium in childhood leukemia research. [unreadable] [unreadable] [unreadable]